Background. Promotion of health is vital for the optimal growth and development of every infant. Globally, many infants died due to common problems such as diarrhoea and respiratory infection; most of these problems are related to inadequate breast feeding, improper complimentary feeding, lack of immunization, and home accident. Infant and child health status depends upon mothers’ knowledge and practice regarding health promotional measures. This study aimed to determine practice and its determinants regarding health promotional measures of infant with 6–12 months age amongst the mothers attending Pediatrics Outpatient Department of Universal College of Medical Science and Teaching Hospital, Bhairahawa, Rupandehi, Nepal. Methods. Hospital-based cross-sectional study was conducted in Universal College of Medical Science, Bhairahawa, Rupandehi, Nepal, among 414 mothers attending pediatrics outpatient department from September 2019–March 2020. Purposive sampling technique was used to select mothers of infants aged 6–12 months. Bivariate analysis was used primarily to assess the association between dependent and independent variables. Variables which were associated in bivariate analysis with
p
<
0.05
were entered into a multivariable logistic regression model to identify associated factors of health promotional measures. The goodness of fit of multivariate logistic regression was checked by Nagelkerke R square and variation inflation factor. Results. The mean age and family size was 25.89 ± 4.81 years and 5.94 ± 2.48, respectively. A total of 71.5% mothers have good practice of health promotional measures. Mothers from Dalit caste (adjusted odds ratio = 0.04, confidence interval: 0.005–0.30), mothers with below school leaving certificate education (AOR = 0.08, CI: 0.02–0.27), fathers engaged in nonagricultural work (AOR = 7.21, CI: 2.59–20.11), birth space of index child greater than 2 years (AOR = 12.88, CI: 3.49–47.58), and family monthly income greater than 20000 Nepalese rupees (AOR = 3.29, CI: 1.16–13.32 were significantly associated with good practice of health promotional measures. Conclusions. More than one-fourth of the mothers have poor practice of health promotional measures. Ethnicity, mothers’ education, fathers’ occupation, birth space of index child, and family monthly income were found to be independent determinants of practice of health promotion measures. Thus, policy makers should provide specific education regarding health promotional measures to both parents.